This invention relates to a new and useful form of an N-substituted 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide amine salt. More particularly, it is concerned with a novel crystalline form of the monoethanolamine salt of N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, which is of especial value in therapy in view of its unique combination of physical, chemical and biological properties.
In the past, various attempts have been made to obtain new and better anti-inflammatory agents. For the most part, these efforts have involved the synthesis and testing of various steroidal compounds such as the corticosteroids or non-steroidal substances of an acidic nature such as phenylbutazone, indomethacin and the like, including the new agent known as piroxicam. The latter substance is a member of a class of anti-inflammatory 4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides described and claimed in U.S. Pat. No. 3,591,584 and is specifically, N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide. In U.S. Pat. No. 4,434,164, there is specifically described and claimed the monoethanolamine salt of N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (piroxicam olamine), which is particularly valuable in pharmaceutical dosage forms as a non-steroidal therapeutic agent for the treatment of painful inflammatory conditions, such as those caused by rheumatoid arthritis, since it is a crystalline, non-hygroscopic, rapidly-dissolving solid with high water solubility. However, in the continuing search for still more improved anti-inflammatory agents, there is a definite need for anti-arthritic agents that possess an even higher degree of chemical stability. For instance, it is to be noted that the monoethanolamine salt product of aforesaid U.S. Pat. No. 4,434,164 formed a degradation product amounting to 0.3-0.6% per year when stored at 30.degree. C. This degradation product will hereinafter be referred to as "the transient impurity" because it decomposes when dissolved in water or methanol.